438 Potentially greater efficacy with CBP-201 for adults with severe vs. moderate atopic dermatitis at baseline: subgroup analyses from the WW001 phase 2 randomized trial

Abstract

Abstract CBP-201 is a next-generation monoclonal antibody targeting the IL-4Rα subunit. Rapid efficacy with CBP-201 was demonstrated in global phase 2 (WW001) and China-only pivotal trials (CN002) in patients with moderate-to-severe atopic dermatitis (AD). Previous studies of AD therapy demonstrated similar efficacy between moderate and severe disease, with a trend toward greater improvement in moderate patients. It is unknown whether there are differences in clinical response to CBP-201 with moderate vs.severe AD. We report post hoc efficacy analyses at Week 16 with CBP-201 300 mg from WW001 in baseline severity subgroups, based on validated Investigator Global Assessment (vIGA™) scores of 3 (moderate) and 4 (severe). In WW001 (NCT04444752), adults with moderate-to-severe AD were enrolled in a RDBPC 16-week trial of subcutaneous CBP-201 or placebo. For post hoc analysis, data for 300 mg every 2- and 4-week dose regimens were pooled. Investigators assessed AD severity using Eczema Area and Severity Index (EASI), SCORing AD (SCORAD), percent Body Surface Area (BSA) of AD involvement and vIGA. Patient-reported outcomes were assessed with the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM). Least squares mean (LSM) score changes were analysed using ANCOVA modeling (including treatment, baseline score and baseline vIGA), with missing data interpolated by last observation carried forward. Responder endpoints were analysed using Clopper–Pearson methodology and, for missing values, nonresponder imputation. P-values are for CBP-201 vs. placebo, per baseline severity subgroup, at Week 16. At baseline, 113 patients had moderate AD (n = 74 CBP-201, n = 39 placebo) and 56 patients had severe AD (n = 39 CBP-201, n = 17 placebo). Baseline EASI scores were lower in the moderate subgroup [mean (SD): CBP-201, 21.5 (7.0); placebo, 22.2 (6.3)] vs. the severe subgroup [CBP-201, 33.6 (11.9); placebo, 31.9 (10.8)]. In both the moderate and severe AD subgroups, significant improvements with CBP-201 vs. placebo were observed. Except for the proportion of patients achieving vIGA 0/1, numerically greater CBP-201 responses were observed in patients with severe vs. moderate AD at Week 16; placebo responses were comparable per subgroup. In the severe and moderate subgroups, LSM SCORAD scores decreased by −42.8% (severe) and −29.8% (moderate), and LSM percent BSA decreased by −29.8% and −17.3%, respectively. Clinically meaningful 2-point improvement in vIGA was reported for 48.7% and 27.0% of patients with severe and moderate AD, respectively. The proportions of patients achieving vIGA 0/1, with 2-point improvement, were 20.5% and 27.0% with severe and moderate AD, respectively. Numerically greater proportions of patients with severe vs. moderate AD experienced EASI responses with CBP-201: EASI-50, 66.7% vs. 54.1%; EASI-75, 53.8% vs. 39.2%; EASI-90, 28.2% vs. 23.0%. Patients with severe vs. moderate AD reported greater improvements in patient reported outcomes with CBP-201: DLQI, −8.7 vs. −7.0; POEM, −12.5 vs. −8.7. Clinically meaningful improvements were observed in patients with AD with either moderate or severe AD after 16 weeks of treatment with CBP-201 300 mg at either 2- or 4-week dosing. There were no differences noted between moderate and severe patients in the placebo treatment group. In most severity readouts, greater proportions of patients with AD with severe disease on study entry experienced clinically meaningful improvements with CBP-201. In future CBP-201 trials, a more severe AD population needs to be examined to determine if this same observation is also noted. Collectively, the WW001 findings support further investigation of CBP-201, at both the 2- and 4-week dosing schedules enrolling larger numbers of moderate and severe patients with AD and with prespecified analyses by baseline AD severity.